Cadmium administration affects circulatory mononuclear cells in rats

Abstract

Although numerous investigations have demonstrated a direct effect of cadmium (Cd) on peripheral blood mononuclear cell (PBMC) activity in humans, there is virtually no data concerning the in vivo impact of this metal on circulatory mononuclear cells. In this study, the effects of a sub-lethal Cd (1 mg/kg) dose were examined in rats 48 h following a single intraperitoneal injection. Cd treatment resulted in increased total peripheral blood leukocyte levels; however, decreases in PBMC numbers were seen. These changes coincided with an accumulation of mononuclear cells in the lungs and an increase in mononuclear cells expressing CD11b. A lack of effect of Cd on spontaneous nitric oxide (NO) production and on iNOS mRNA levels in the PBMC was also noted. Differential effects of Cd on PBMC inflammatory cytokine (IL-1β, TNFα, IL-6, IFNγ, and IL-17) gene expression and production were also seen. Specifically, except for IL-1β (levels increased), there were decreases (relative to controls) in mRNA levels for all the other cytokines examined. While there were no Cd treatment-related changes in spontaneous production of the cytokines assessed, there seemed to be a trend (p = 0.06) toward a decrease in spontaneous IL-6 release. When these harvested cells were stimulated ex vivo, there was no effect from Cd exposure on LPS-stimulated IL-1β and TNFα or on ConA-stimulated IFNγ or IL-17 production, but a decrease in IL-6 production in response to LPS was, again, noted. A preliminary study with a lower Cd dose (0.5 mg/kg) revealed some of the same outcomes noted here (mononuclear cell infiltration into lungs, increases in PBMC IL-1β mRNA levels), but differential (increased IL-17 mRNA levels) or newly detected outcomes (increased levels of IL-1α mRNA) as well. The described effects of the single in vivo exposure to Cd on PBMC might contribute to a better overall understanding of the immunomodulatory potential of this environmental contaminant.

Acute cadmium administration to rats exerts both immunosuppressive and proinflammatory effects in spleen

“…The reason for these differences is not clear, but show variable effects of Cd on this cytokine. Results from the present study are in line with increases in IL-1b mRNA in PBMC of rats treated with higher Cd dose (Djokic et al, 2014b) and point out this cytokine as important target for Cd. Increases in IL-1b (as well as IL-1a at higher Cd dose) underline the significance of this cytokine in Cd-induced responses in spleen.…”

“…Together with our previous study that showed effect of Cd administration in rats on PBMC expression of IL-17 (Djokic et al, 2014b) data from the present study imply that IL-17 might be target for Cd.…”

Chronic Cadmium Exposure Alters Cardiac Matrix Metalloproteinases in the Heart of Sprague-Dawley Rat

“…Extensive research exploring the impact of cadmium along the inflammation axis have reported the production and upregulation of IL-6, TNF-α and IL-1β both in vivo and in vitro ( Djokic et al, 2015 ; Ninkov et al, 2015 ; Tucovic et al, 2018 ). In this study, the pro-inflammatory impact of the cadmium treatment was also observed as an upregulation in pro-inflammatory cytokines- IL-6 and IL-1β.…”

Cadmium Toxicity: Oxidative Stress, Inflammation and Tissue Injury

“…A later study by Djokic et al, reported differential effects of a single sub-lethal Cd dose (1 mg/kg b.w.) on rat PMN cell biology [74]. While there was a limited effect of high dose Cd on the spontaneous production of TNF-α despite an increase in the basal mRNA level, there seemed a tendency for decreased spontaneous production of IL-6 with a decrease in mRNA levels.…”